The flea and the tiger face off in La Liga
World Player of the Year Messi, nicknamed 'the flea', extended his record goals haul for 2012 to 88 with a double in the King's Cup on Wednesday and the Argentine tops the La Liga scoring chart on 23 from 15 matches.
Falcao, known as 'the tiger' and coveted by several of Europe's richest clubs, became the first player in more than 10 years to score five in a 6-0 La Liga thrashing of Deportivo La Coruna last weekend, taking his tally for the season to 16.
The pair have very different playing styles, with the 25-year-old Messi often finding the net after weaving runs from outside the penalty area that leave opposition defenders floundering.
Colombian Falcao, 26, is more of a traditional striker who operates inside the box to devastating effect.
A 15th win in 16 matches for Barca at the Nou Camp would stretch their lead over Atletico to nine points.
Defeat for Atletico would put third-placed champions Real Madrid within two points of their city rivals if they beat struggling Espanyol at the Bernabeu two hours earlier.
Real forward Cristiano Ronaldo, the world's most expensive player, has been left in the shade by Messi and Falcao in recent weeks and has 13 goals in third spot on the scoring chart.
Spain coach Vicente del Bosque said the presence of the goal-hungry trio in La Liga was "great news" for Spanish football and soccer fans in the Iberian nation were fortunate to be able to enjoy them in the flesh.
"The three are different, the only thing they have in common is goals," Del Bosque was quoted as saying in daily newspaper El Pais on Monday.
"The three start from different positions," added the former Real coach.
"Falcao is the goal-scorer inside the box par excellence. Cristiano is more a player who operates down the wing in search of goals and Messi just goes wherever he wants.
"They are the undisputed reference points for their teams."
Messi has stolen most of the recent headlines after he broke Gerd Muller's 40-year-old record for the most goals scored in a calendar year of 85.
He has Saturday's home game against Atletico and the match at Real Valladolid to add to his tally and is hot favourite to secure an unprecedented fourth straight World Player award when the winner is announced next month.
"Messi is unique because he is already the best player in the history of this sport," his Barca and Argentina team mate Javier Mascherano said after Wednesday's 2-0 Cup victory at second-division Cordoba.
"We are talking about 88 goals as if it were something normal but what he has done is incredible," he added. "This is a lad who has been touched by a magic wand."
Malaga will look to cement their hold on fourth and a Champions League qualification berth when they play erratic Sevilla in Saturday's Andalusia derby.
Ernesto Valverde has won his opening two games since taking over from the sacked Mauricio Pellegrino at Valencia and will seek to make it three out of three when his side host Rayo Vallecano on Sunday.